Pulmonary surfactant is a complex mixture of lipids and proteins that prevents collapse of the alveoli and distal airways at low lung volumes. Silica dust causes a massive increase in the surfactant content of the lungs but the mechanisms through which this occurs are not known. Examination of the rates at which surfactant phospholipids are synthesized, secreted, and cleared from the lungs of silica-treated rats revealed that expansion of the intra and extracellular pools of surfactant could be accounted for by imbalances between the rates at which surfactant phospholipids are synthesized by alveolar Type II cells, secreted, and then cleared from the alveoli. Under normal circumstances these rates of synthesis, secretion, and clearance are the same the intra- and extra-cellular pools of surfactant do not change in size. Our studies further indicated that some, but not all Type II cells, were substantially increased in size. We hypothesize that the expanded surfactant pools are related to the appearance of these hypertrophic Type II cells. By using protease digestion and centrifugal elutriation procedures we have now succeeded in isolating hypertrophic Type II cells from the lungs of silica-treated rats and preliminary evidence indicates that these cells are hyperactive in their ability to synthesize surfactant. In future studies we will further characterize the changes that have occurred in the silica-exposed Type II cells and identify which steps in the biosynthetic pathway are responsible for the increased rate of biosynthesis of surfactant phospholipids. We will also investigate phospholipid biosynthesis in Type II cells under conditions of in vitro cultivation as a means of elucidating the mechanisms through which surfactant biosynthesis is affected by silica.